Virological

Take this with a grain of salt, copied from reddit:

Read this website:

http://virological.org/

Specifically this one:

http://virological.org/t/ncovs-relationship-to-bat-coronaviruses-recombination-signals-no-snakes/331

and this one:

http://virological.org/t/missed-orfs-in-ncov/345

Basically

Wuhan virus is essentially SARs

http://virological.org/t/missed-orfs-in-ncov/345

"Anyone notice two ‘accessory’ ORFs not annotated in nCoV? Orf13 (aka 9b) (28284:28577) and Orf14 (28734:28955) . One is ~ 70% ID and other ~ 90% to syntenous ORFs in BAT SARS 2017 ?"

Translation:

Some very specific parts of the genome are matching almost exactly, which only occurs in almost identical viruses. The ORFs are tagged parts of genes, this researcher is discussing how Chinese researchers "omitted" parts of their gene annotation. Some back story is the gene sequences have been shared openly so they can be studied, Chinese messed with how they annotated the sequences.

To understand this better, here is the wikipedia definition of 'accessory gene' (ORF is just a chunk of the gene):

"The variable or accessory genome (also: flexible, dispensable genome) refers to genes not present in all strains of a species. These include genes present in two or more strains or even genes unique to a single strain only, for example, genes for strain specific adaptation such as antibiotic resistance."

The researcher is saying specific strain markers are matching between the 2017 virus and this one. Which…

This seems pretty outdated -- The Wuhan market and (proximity to the Disease Research center) has been IDed as the primary place where it spread, but is no longer considered the place where it originated. That's why we're still looking into the origins of this thing.

The first case IDed by the Lancet had no exposure to the seafood market, but many later cases did (pg 499):

https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930183-5

A decent preprint from the US looking at the genetic origins:

http://virological.org/t/the-proximal-origin-of-sars-cov-2/398

> It is improbable that SARS-CoV-2 emerged through laboratory manipulation of an existing SARS-related coronavirus. As noted above, the RBD of SARS-CoV-2 is optimized for human ACE2 receptor binding with an efficient binding solution different to that which would have been predicted. Further, if genetic manipulation had been performed, one would expect that one of the several reverse genetic systems available for betacoronaviruses would have been used. However, this is not the case as the genetic data shows that SARS-CoV-2 is not derived from any previously used virus backbone17. Instead, we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: (i) natural selection in a non-human animal host prior to zoonotic transfer, and (ii) natural selection in humans following zoonotic transfer. We also discuss whether selection during passage in culture could have given rise to the same observed…

This Week in Virology has debunked the claims that there multiple strains of the virus that are either more transmissible, or more or less severe, or that your immune system would react differently to.

Here is what they had to say in episode 590[1]:

Vincent Racaniello: There are a series of articles here, where there have been some claims about different circulating lineages and what that means. Are you on this, Cathy?

Cathy Spindler: Right. So, there was an article that I first saw in the LA Times "Chinese Scientists Say Second Coronavirus Strain Is More Dangerous"[2]. But in that there's a link to virological.org, which we talked about another article posted there a couple of weeks ago[3], and they really debunk this and think even that this Chinese article about a second Coronavirus should be retracted. Two of the key claims that are reached by misunderstanding and overinterpreation of data and an additional analysis suffers from methodological limitations. So this long thing on virological.org goes in to the reasons why there's no real evidence for two different strains, a more severe strain and a less severe strain.

Rich Condit: It also provides a nice summary of this sort of variation in sequence that's being observed in the virus over time, which is good.

Vincent: Yeah, it's a good article. We'll put a link. It's worth reading, but as everyone should know, when these [indistinct] viruses, every replication cycle they sustain mutations in their genomes and the…

For those (like me) who are looking for some more details of this new strain, I found 2 papers from the `COVID-19 Genomics Consortium UK (CoG-UK)` of great interest. It seems like the prime reasons for concern are increased frequency of mutations, increased proportion of cases, and possible change in immune response

> Several aspects of this cluster are noteworthy for epidemiological and biological reasons and we report preliminary findings below. In summary:
The B.1.1.7 lineage accounts for an increasing proportion of cases in parts of England. The number of B.1.1.7 cases, and the number of regions reporting B.1.1.7 infections, are growing.
B.1.1.7 has an unusually large number of genetic changes, particularly in the spike protein.
Three of these mutations have potential biological effects that have been described previously to varying extents:

> - Mutation N501Y is one of six key contact residues within the receptor-binding domain (RBD) and has been identified as increasing binding affinity to human and murine ACE2.

> - The spike deletion 69-70del has been described in the context of evasion to the human immune response but has also occurred a number of times in association with other RBD changes.

> - Mutation P681H is immediately adjacent to the furin cleavage site, a known location of biological significance.

> The rapid growth of this lineage indicates the need for enhanced genomic and epidemiological surveillance worldwide and laboratory investigations of…

One of the "interesting" things about the new strain is that generally there is genetic drift happening all the time with the virus and you can trace it internationally into a sort of 'family tree'. This can be used to work out how it is spreading geographically, its like a fingerprint that changes as it spreads.

e.g. the tree diagrams in this tweet: https://twitter.com/firefoxx66/status/1340359989395861506

The new strain is notable because it has no obvious ancestors - it has about 14 or so changes that can't be traced backwards in the tree. This points to it arising within one immunocompromised individual.

See https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563

"The accrual of 14 lineage-specific amino acid replacements prior to its detection is, to date, unprecedented in the global virus genomic data for the COVID-19 pandemic."

"These considerations lead us to hypothesise that the unusual genetic divergence of lineage B.1.1.7 may have resulted, at least in part, from virus evolution with a chronically-infected individual. Although such infections are rare, and onward transmission from them presumably even rarer, they are not improbable given the ongoing large number of new infections."

In all of this, its worth remembering we've never tracked an epidemic in this much detail before, so perhaps this sort of thing is just par for the course.

This article is very light on details.

Here’s a better one:

“Update on new SARS-CoV-2 variant and how COG-UK tracks emerging mutations” Dec 14, 2020
https://www.cogconsortium.uk/news_item/update-on-new-sars-cov-2-variant-and-how-cog-uk-tracks-emerging-mutations/

Edit: Here’s a report:

“Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations”

Recently a distinct phylogenetic cluster (named lineage B.1.1.7) was detected within the COG-UK surveillance dataset. This cluster has been growing rapidly over the past 4 weeks and since been observed in other UK locations, indicating further spread.

Several aspects of this cluster are noteworthy for epidemiological and biological reasons and we report preliminary findings below. In summary:
• The B.1.1.7 lineage accounts for an increasing proportion of cases in parts of England.

• The number of B.1.1.7 cases, and the number of regions reporting B.1.1.7 infections, are growing.

• B.1.1.7 has an unusually large number of genetic changes, particularly in the spike protein.

https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563